{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T12:43:07Z","timestamp":1792068187226,"version":"4.4.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005860","name":"Helsefonden","doi-asserted-by":"publisher","award":["21-B-0437"],"award-info":[{"award-number":["21-B-0437"]}],"id":[{"id":"10.13039\/501100005860","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010352","name":"Helen Rudes Fond","doi-asserted-by":"publisher","award":["60988"],"award-info":[{"award-number":["60988"]}],"id":[{"id":"10.13039\/501100010352","id-type":"DOI","asserted-by":"publisher"}]},{"name":"A & J C Tvergaards Fond"},{"DOI":"10.13039\/501100010363","name":"Minister Erna Hamiltons Legat for Videnskab og Kunst","doi-asserted-by":"publisher","award":["24-2022"],"award-info":[{"award-number":["24-2022"]}],"id":[{"id":"10.13039\/501100010363","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Clinical features applicable to the entire spectrum of viral meningitis are limited, and prognostic factors for adverse outcomes are undetermined.<\/jats:p>\n                  <jats:p>This nationwide population-based prospective cohort study included all adults with presumed and microbiologically confirmed viral meningitis in Denmark from 2015 until 2020. Prognostic factors for an unfavourable outcome (Glasgow Outcome Scale score of 1\u20134) 30 days after discharge were examined by modified Poisson regression.<\/jats:p>\n                  <jats:p>In total, 1066 episodes of viral meningitis were included, yielding a mean annual incidence of 4.7 episodes per 100 000 persons. Pathogens were enteroviruses in 419\/1066 (39%), herpes simplex virus type 2 in 171\/1066 (16%), varicella-zoster virus in 162\/1066 (15%), miscellaneous viruses in 31\/1066 (3%) and remained unidentified in 283\/1066 (27%). The median age was 33 years (IQR 27\u201344), and 576\/1066 (54%) were females. In herpes simplex virus type 2 meningitis, 131\/171 (77%) were females. Immunosuppression [32\/162 (20%)] and shingles [90\/149 (60%)] were frequent in varicella-zoster virus meningitis. The triad of headache, neck stiffness and hyperacusis or photophobia was present in 264\/960 (28%). The median time until lumbar puncture was 3.0 h (IQR 1.3\u20137.1), and the median CSF leucocyte count was 160 cells\/\u00b5l (IQR 60\u2013358). The outcome was unfavourable in 216\/1055 (20%) 30 days after discharge. Using unidentified pathogen as the reference, the adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 0.95\u20131.88) for enteroviruses, 1.55 (95% CI 1.00\u20132.41) for herpes simplex virus type 2, 1.51 (95% CI 0.98\u20132.33) for varicella-zoster virus and 1.37 (95% CI 0.61\u20133.05) for miscellaneous viruses. The adjusted relative risk of an unfavourable outcome was 1.34 (95% CI 1.03\u20131.75) for females. Timing of acyclovir or valacyclovir was not associated with the outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.<\/jats:p>\n                  <jats:p>In summary, the outcome of viral meningitis was similar among patients with different aetiologies, including those with presumed viral meningitis but without an identified pathogen. Females had an increased risk of an unfavourable outcome. Early antiviral treatment was not associated with an improved outcome in meningitis caused by herpes simplex virus type 2 or varicella-zoster virus.<\/jats:p>","DOI":"10.1093\/brain\/awad089","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T14:39:25Z","timestamp":1678977565000},"page":"3816-3825","source":"Crossref","is-referenced-by-count":45,"title":["Clinical features and prognostic factors in adults with viral meningitis"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4113-4182","authenticated-orcid":false,"given":"Pelle Trier","family":"Petersen","sequence":"first","affiliation":[{"name":"Department of Pulmonary and Infectious Diseases, Nordsj\u00e6llands Hospital , 3400 Hiller\u00f8d , Denmark"},{"name":"Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7398-814X","authenticated-orcid":false,"given":"Jacob","family":"Bodilsen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Aalborg University Hospital , 9000 Aalborg , Denmark"},{"name":"Department of Clinical Medicine, Aalborg University , 9000 Aalborg , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha Phill Gr\u00f8nholm","family":"Jepsen","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Infectious Diseases, Nordsj\u00e6llands Hospital , 3400 Hiller\u00f8d , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lykke","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Odense University Hospital , 5000 Odense , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merete","family":"Storgaard","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Aarhus University Hospital , 8200 Aarhus , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgitte R\u00f8nde","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hvidovre Hospital , 2650 Hvidovre , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jannik","family":"Helweg-Larsen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Rigshospitalet , 2100 Copenhagen , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-1743","authenticated-orcid":false,"given":"Lothar","family":"Wiese","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sj\u00e6llands University Hospital , 4000 Roskilde , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Rudolf","family":"L\u00fcttichau","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Herlev Hospital , 2730 Herlev , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian \u00d8stergaard","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Hvidovre Hospital , 2650 Hvidovre , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0841-8255","authenticated-orcid":false,"given":"Henrik","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Aalborg University Hospital , 9000 Aalborg , Denmark"},{"name":"Department of Clinical Medicine, Aalborg University , 9000 Aalborg , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian Thomas","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sj\u00e6llands University Hospital , 4000 Roskilde , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Danish Study Group of Infections of the Brain (DASGIB)","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,16]]},"reference":[{"key":"2023090117342341000_awad089-B1","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/S1473-3099(18)30245-7","article-title":"Incidence, aetiology, and sequelae of viral meningitis in UK adults: A multicentre prospective observational cohort study","volume":"18","author":"McGill","year":"2018","journal-title":"Lancet Infect Dis"},{"key":"2023090117342341000_awad089-B2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1212\/01.wnl.0000191407.81333.00","article-title":"Etiology of aseptic meningitis and encephalitis in an adult population","volume":"66","author":"Kupila","year":"2006","journal-title":"Neurology"},{"key":"2023090117342341000_awad089-B3","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1080\/00365540802235741","article-title":"High diagnostic yield by CSF-PCR for entero- and herpes simplex viruses and TBEV serology in adults with acute aseptic meningitis in Stockholm","volume":"40","author":"Franzen-R\u00f6hl","year":"2008","journal-title":"Scand J Infect Dis"},{"key":"2023090117342341000_awad089-B4","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/jmv.23470","article-title":"Viral infections of the central nervous system in Spain: A prospective study","volume":"85","author":"de Ory","year":"2013","journal-title":"J Med Virol"},{"key":"2023090117342341000_awad089-B5","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1007\/s15010-017-0993-4","article-title":"A retrospective study of viral central nervous system infections: Relationship amongst aetiology, clinical course and outcome","volume":"45","author":"Calleri","year":"2017","journal-title":"Infection"},{"key":"2023090117342341000_awad089-B6","doi-asserted-by":"crossref","first-page":"16158","DOI":"10.1038\/s41598-019-52570-2","article-title":"Encephalitis and aseptic meningitis: Short-term and long-term outcome, quality of life and neuropsychological functioning","volume":"9","author":"Quist-Paulsen","year":"2019","journal-title":"Sci Rep"},{"key":"2023090117342341000_awad089-B7","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1093\/brain\/awh711","article-title":"Neuropsychological sequelae of bacterial and viral meningitis","volume":"129","author":"Schmidt","year":"2006","journal-title":"Brain"},{"key":"2023090117342341000_awad089-B8","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1136\/jnnp.2005.071142","article-title":"Sleep disorders are long-term sequelae of both bacterial and viral meningitis","volume":"77","author":"Schmidt","year":"2006","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2023090117342341000_awad089-B9","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1007\/s004150200064","article-title":"Mild cognitive impairment after viral meningitis in adults","volume":"249","author":"Sittinger","year":"2002","journal-title":"J Neurol"},{"key":"2023090117342341000_awad089-B10","doi-asserted-by":"crossref","first-page":"921","DOI":"10.2147\/CLEP.S326461","article-title":"Existing data sources for clinical epidemiology: The Danish Study Group of Infections of the Brain Database (DASGIB)","volume":"13","author":"Bodilsen","year":"2021","journal-title":"Clin Epidemiol"},{"key":"2023090117342341000_awad089-B11","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1093\/cid\/cit458","article-title":"Case definitions, diagnostic algorithms, and priorities in encephalitis: Consensus statement of the international encephalitis consortium","volume":"57","author":"Venkatesan","year":"2013","journal-title":"Clin Infect Dis"},{"key":"2023090117342341000_awad089-B12","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1093\/cid\/ciab1071","article-title":"Herpes simplex virus 2 meningitis in adults: A prospective, nationwide, population-based cohort study","volume":"75","author":"Jakobsen","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2023090117342341000_awad089-B13","doi-asserted-by":"crossref","first-page":"e454","DOI":"10.1212\/WNL.0000000000012294","article-title":"Enterovirus meningitis in adults: A prospective nationwide population-based cohort study","volume":"97","author":"Bodilsen","year":"2021","journal-title":"Neurology"},{"key":"2023090117342341000_awad089-B14"},{"key":"2023090117342341000_awad089-B15","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1093\/aje\/kwh090","article-title":"A modified Poisson regression approach to prospective studies with binary data","volume":"159","author":"Zou","year":"2004","journal-title":"Am J Epidemiol"},{"key":"2023090117342341000_awad089-B16","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1056\/NEJMoa040845","article-title":"Clinical features and prognostic factors in adults with bacterial meningitis","volume":"351","author":"van de Beek","year":"2004","journal-title":"N Engl J Med"},{"key":"2023090117342341000_awad089-B17","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S1473-3099(15)00430-2","article-title":"Community-acquired bacterial meningitis in adults in The Netherlands, 2006\u201314: A prospective cohort study","volume":"16","author":"Bijlsma","year":"2016","journal-title":"Lancet Infect Dis"},{"key":"2023090117342341000_awad089-B18","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1089\/neu.1998.15.573","article-title":"Structured interviews for the Glasgow Outcome Scale and the extended Glasgow Outcome Scale: Guidelines for their use","volume":"15","author":"Wilson","year":"1998","journal-title":"J Neurotrauma"},{"key":"2023090117342341000_awad089-B19","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/qjmed\/hcq121","article-title":"Acute central nervous system infections in adults--a retrospective cohort study in the NHS North West region","volume":"103","author":"Michael","year":"2010","journal-title":"QJM"},{"key":"2023090117342341000_awad089-B20","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1056\/NEJMoa010399","article-title":"Computed tomography of the head before lumbar puncture in adults with suspected meningitis","volume":"345","author":"Hasbun","year":"2001","journal-title":"N Engl J Med"},{"key":"2023090117342341000_awad089-B21","doi-asserted-by":"crossref","first-page":"745","DOI":"10.2147\/CLEP.S256838","article-title":"Long-term survival, morbidity, social functioning and risk of disability in patients with a herpes simplex virus type 1 or type 2 central nervous system infection, Denmark, 2000\u20132016","volume":"12","author":"Hansen","year":"2020","journal-title":"Clin Epidemiol"},{"key":"2023090117342341000_awad089-B22","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1093\/infdis\/jiaa151","article-title":"Long-term survival, health, social functioning, and education in patients with an enterovirus central nervous system infection, Denmark, 1997\u20132016","volume":"222","author":"Omland","year":"2020","journal-title":"J Infect Dis"},{"key":"2023090117342341000_awad089-B23","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1038\/s41591-022-01810-6","article-title":"Unexplained post-acute infection syndromes","volume":"28","author":"Choutka","year":"2022","journal-title":"Nat Med"},{"key":"2023090117342341000_awad089-B24","doi-asserted-by":"crossref","first-page":"2409","DOI":"10.1128\/AAC.00227-06","article-title":"Enteroviral meningitis: Natural history and outcome of pleconaril therapy","volume":"50","author":"Desmond","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"key":"2023090117342341000_awad089-B25","first-page":"106","article-title":"Gender differences in community-acquired meningitis in adults: Clinical presentations and prognostic factors","volume":"1","author":"Dharmarajan","year":"2016","journal-title":"J Meningitis"},{"key":"2023090117342341000_awad089-B26","doi-asserted-by":"crossref","first-page":"121.e9","DOI":"10.1016\/j.cmi.2016.10.026","article-title":"Sex-based differences in adults with community-acquired bacterial meningitis: A prospective cohort study","volume":"23","author":"Dias","year":"2017","journal-title":"Clin Microbiol Infect"},{"key":"2023090117342341000_awad089-B27","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1002\/bies.201200099","article-title":"Sex influences immune responses to viruses, and efficacy of prophylaxis and therapeutic treatments for viral diseases","volume":"34","author":"Klein","year":"2012","journal-title":"Bioessays"},{"key":"2023090117342341000_awad089-B28","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s15010-015-0791-9","article-title":"Sex differences in immune responses to infectious diseases","volume":"43","author":"Fischer","year":"2015","journal-title":"Infection"},{"key":"2023090117342341000_awad089-B29","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.720952","article-title":"Sex differences in immunity to viral infections","volume":"12","author":"Jacobsen","year":"2021","journal-title":"Front Immunol"},{"key":"2023090117342341000_awad089-B30","author":"Lebech","year":"2018"},{"key":"2023090117342341000_awad089-B31","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1080\/00365540701509881","article-title":"Herpes simplex virus type 2 infections of the central nervous system: A retrospective study of 49 patients","volume":"40","author":"Omland","year":"2008","journal-title":"Scand J Infect Dis"},{"key":"2023090117342341000_awad089-B32","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1002\/jmv.23999","article-title":"Comparison of clinical manifestations, outcomes and cerebrospinal fluid findings between herpes simplex type 1 and type 2 central nervous system infections in adults","volume":"86","author":"Moon","year":"2014","journal-title":"J Med Virol"},{"key":"2023090117342341000_awad089-B33","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1093\/cid\/ciu772","article-title":"The role of antiviral therapy in immunocompromised patients with herpes simplex virus meningitis","volume":"60","author":"Noska","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2023090117342341000_awad089-B34","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1086\/379520","article-title":"Herpes simplex virus type 2 as a cause of severe meningitis in immunocompromised adults","volume":"37","author":"Momm\u00e9ja-Marin","year":"2003","journal-title":"Clin Infect Dis"},{"key":"2023090117342341000_awad089-B35","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S0140-6736(75)92830-5","article-title":"Assessment of outcome after severe brain damage a practical scale","volume":"305","author":"Jennett","year":"1975","journal-title":"Lancet"},{"key":"2023090117342341000_awad089-B36","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/S1473-3099(10)70222-X","article-title":"Causes of encephalitis and differences in their clinical presentations in England: A multicentre, population-based prospective study","volume":"10","author":"Granerod","year":"2010","journal-title":"Lancet Infect Dis"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/brain\/advance-article-pdf\/doi\/10.1093\/brain\/awad089\/50169246\/awad089.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/146\/9\/3816\/51330541\/awad089.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/brain\/article-pdf\/146\/9\/3816\/51330541\/awad089.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T13:37:20Z","timestamp":1693575440000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/146\/9\/3816\/7079005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,16]]},"references-count":36,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,3,16]]},"published-print":{"date-parts":[[2023,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awad089","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,9]]},"published":{"date-parts":[[2023,3,16]]}}}